3-O-sulfated heparan sulfate proteoglycan (3-OS HSPG)

3-O-sulfated heparan sulfate proteoglycans (3-OS HSPGs) are a specialized subset of heparan sulfate proteoglycans characterized by a rare 3-O-sulfation modification on the glucosamine residues of the heparan sulfate (HS) chains (Source 1.2.1, 1.3.3). This modification is catalyzed by a family of enzymes known as heparan sulfate 3-O-sulfotransferases (HS3STs) (Source 1.2.1). 3-OS HSPGs play a critical role in blood coagulation by providing the high-affinity binding site for antithrombin III, which is essential for the anticoagulant activity of heparin and fondaparinux (Source 1.3.1, 1.3.3). Beyond coagulation, they serve as key cell surface receptors for the entry of Herpes Simplex Virus type 1 (HSV-1) by interacting with the viral envelope glycoprotein D (gD) (Source 1.1.1, 1.4.2). Recent research also implicates 3-OS HSPGs in the pathogenesis of Alzheimer's disease, where they facilitate the cellular uptake and transcellular spreading of tau aggregates (Source 1.2.2, 1.3.5). In cancer, the expression of HS3STs is often dysregulated, influencing tumor cell proliferation, migration, and angiogenesis (Source 1.2.1, 1.3.4). Consequently, 3-OS HSPGs and the enzymes responsible for their synthesis are emerging as significant therapeutic targets for antiviral, anticoagulant, and neuroprotective interventions (Source 1.2.3, 1.3.2).

Other names

3-O-sulfated heparan sulfate3-OS HS3-O-S HSPG3-O-sulfated HSGlucosaminyl 3-O-sulfated heparan sulfate

3-O-sulfated heparan sulfate proteoglycans (3-OS HSPGs) function as specific docking sites for various ligands. In the coagulation cascade, the 3-O-sulfate group within a specific pentasaccharide sequence binds antithrombin III, inducing a conformational change that accelerates the inhibition of Factor Xa and thrombin (Source 1.3.3). In viral infections, specifically HSV-1, the 3-OS motif acts as a co-receptor for the viral glycoprotein D (gD), facilitating membrane fusion and viral entry (Source 1.1.1, 1.4.2). In neurodegenerative contexts, 3-OS HSPGs mediate the endocytosis of tau aggregates, promoting their intracellular accumulation and spread (Source 1.2.2, 1.3.5). Therapeutic strategies involve using synthetic mimetics to compete for these binding sites or inhibiting the sulfotransferase enzymes (HS3STs) to prevent the formation of the 3-OS motif (Source 1.2.3).